The proposed project aims to analyze various aspects of the morphology and physiology of mammalian extraocular muscles. For this purpose the in vitro preparation of the inferior rectus muscle of the rat which was developed previously is being used. We proposed to study morphologically the various cellular populations present in the muscle and their distribution in the global and orbital layers and to verify if systematic morphological variability is present or not anong the fiber length. Using a combined electrophysiological-morphological approach we plan to study the electrical properties and synaptic activity of muscle fibers to correlate function with morphology. A protocol for intracellular labeling of fibers and subsequent staining of nerve endings recently developed is used for the latter purpose. Previous examination of the electrical properties and synaptic activities has shown that most of the fibers are typical singly innervated or twitch fibers while a minority is multiply innervated and equivalent to tonic fibers of amphibians. We shall attempt to correlate the physiological properties of these cell types with their morphological structure. The study proposes also to examine the metabolic requirements of the tension evoked in tonic fibers by cholinomimetics and elevated (K). Until now we have observed that brief exposures (2-5 min) to hypoxic saline or to salines containing Na azide produce a sudden decrease in the tension output of multiply innervated fibers. However, longer exposures (10-12 min) to these modified salines induce a potentiation of tension and a reduction of the rate of relaxation. Experiments designed to analyze the effects of cyanide and other metabolic inhibitors and the quantitative relationship between 02 tension and contractility are planned.